These studies are designed to determine, in experimental animals and humans, the ability of various substances to induce HbF synthesis. Several drugs have been shown to have this potential. Because of its safety and demonstrated activity, we have initiated a expanded phase I-II study of Hydroxyurea. The purpose of this study is to further define the frequency and magnitude of response of individual patients and to identify significant toxicity. During the past several years, various hematopoietic growth factors have been molecularly cloned and large amounts have been synthesized in vitro. Several factors are now available for clinical testing. Those with activity on the erythroid progenitor and precursor population have the potential for stimulating HbF synthesis. Studies in Rhesus monkeys have been designed to test these substances. To date we have learned that erythropoietin has a definite, although limited ability to initiate HbF synthesis.